Toll-like receptor agonists partially restore the production of pro-inflammatory cytokines and type I interferon in Sezary syndrome

Autor(es):Mostrar menos -

Manfrere, Kelly C. G. ; Torrealba, Marina P. ; Miyashiro, Denis R. ; Oliveira, Luanda M. S. ; de Carvalho, Gabriel C. ; Lima, Josenilson F. ; Branco, Anna Claudia C. C. ; Pereira, Ntalli Z. ; Pereira, Juliana ; Sanches, Jr., Jose A. ; Sato, Maria N.

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 7, n. 46, p. 74592-74601, NOV 15 2016.
• Citações Web of Science: 4

Resumo

Sezary syndrome (SS) carries a poor prognosis, and infections represent the most frequent cause of death in SS patients. Toll-like receptors (TLRs) are a family of innate immune receptors that induce protective immune responses against infections. We sought to evaluate the ability of TLR agonists to induce inflammatory cytokine, Th2 cytokine, and type I interferon (IFN-I) production by peripheral blood mononuclear cells (PBMC) of untreated SS patients. We detected impaired IL-6, IL-10 and IL-13 secretion by PBMC induced by the agonists for TLR5, TLR3, TLR7 and TLR9 in SS patients, while it was partially recovered by TLR2/TLR4 and TLR7/8 agonists TNF secretion was restored following stimulation with TLR2/TLR4 agonists. IFN-gamma was scarcely produced upon TLR activation in SS cells, albeit TLR 7/8 (CL097) enhanced their secretion at lower levels than the control group. TLR9 agonist efficiently induced IFN-I in SS patients, although this positive regulation was not observed for other cytokines, in direct contrast to the broad activity of CL097. Among the TLR agonists, TLR4 was able to induce pro-inflammatory, IL-10 and Th2 secretion, while TLR7-8 agonist induced the inflammatory cytokines, IFN-I and IFN-gamma. These findings reveal a dysfunctional cytokine response upon both extracellular and intracellular TLR activation in SS patients, which was partially restored by TLRs agonists. (AU)

• Processo FAPESP: 14/04865-9 - Ativação da resposta citotóxica mediada pelas células natural killer e TCD8+ polifuncionais por agonistas de receptores toll-like na micose fungóide e síndrome de Sézary
• Beneficiário: José Antonio Sanches Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular